Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2020 Dec 3;23(9):581-586.
doi: 10.1093/ijnp/pyaa046.

Serum VEGF Predicts Clinical Improvement Induced by Cerebrolysin Plus Donepezil in Patients With Advanced Alzheimer's Disease

X Anton Alvarez  1   2 , Irene Alvarez  1 , Antia Martinez  3 , Iria Romero  1   2 , Concha Benito  1 , Irene Suarez  1 , Silvia Mourente  4 , Manuel Fantini  5 , Jesús Figueroa  1   6 , Manuel Aleixandre  7 , Carlos Linares  8 , Dafin Muresanu  9 , Stefan Winter  10 , Herbert Moessler  11
Affiliations

Serum VEGF Predicts Clinical Improvement Induced by Cerebrolysin Plus Donepezil in Patients With Advanced Alzheimer's Disease

X Anton Alvarez et al. Int J Neuropsychopharmacol. .

Abstract

Serum vascular endothelial growth factor (VEGF) increases with Alzheimer's disease (AD) severity and may prevent cognitive decline. However, information on the influence of AD drug therapy on circulating VEGF is limited. This study assessed changes in serum VEGF levels and its association with clinical and functional responses in mild to moderate AD patients who were treated with Cerebrolysin, donepezil, or the combined therapy in a randomized, controlled trial. Treatment with Cerebrolysin plus donepezil reduced elevated serum VEGF levels and improved functioning and cognition significantly compared with donepezil alone in patients with advanced AD, and treatment differences were more pronounced in patients with higher VEGF levels. Our results indicate that the combined therapy reversed the increase of serum VEGF in advanced AD, which was associated with cognitive and functional responses, particularly in patients with high baseline VEGF.

Keywords: Alzheimer’s disease (AD); Cerebrolysin; combined therapy; donepezil; vascular endothelial growth factor (VEGF).

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Effects of Cerebrolysin, donepezil and the combination therapy on: (a) serum VEGF levels (VEGFnL: vascular endothelial growth factor natural log), (b) cognitive performance (ADAS-cog+: AD Assessment Scale-cognitive subscale plus), and (c) functioning (ADCS-ADL: AD Cooperative Study-Activities of Daily Living Scale) at week 16 (end of active Cerebrolysin treatment) and at week 28 (end of the study) in patients with advanced Alzheimer’s disease (AD). (a) *P < .05 and **P < .01 versus donepezil group; (b) *P < .05 versus Donepezil group; (c) *P < .05 and **P < .01 vs donepezil and Cerebrolysin groups. Data are presented as LS mean (± SE).
See this image and copyright information in PMC

References

    1. Alvarez XA, Sampedro C, Cacabelos R, Linares C, Aleixandre M, García-Fantini M, Moessler H (2009) Reduced TNF-α and increased IGF-I levels in the serum of Alzheimer’s disease patients treated with the neurotrophic agent cerebrolysin. Int J Neuropsychopharmacol 12:867–872. - PubMed
    1. Alvarez XA, Cacabelos R, Sampedro C, Aleixandre M, Linares C, Granizo E, Doppler E, Moessler H (2011a) Efficacy and safety of Cerebrolysin in moderate to moderately severe Alzheimer’s disease: results of a randomized, double-blind, controlled trial investigating three dosages of Cerebrolysin. Eur J Neurol 18:59–68. - PubMed
    1. Alvarez XA, Cacabelos R, Sampedro C, Couceiro V, Aleixandre M, Vargas M, Linares C, Granizo E, García-Fantini M, Baurecht W, Doppler E, Moessler H (2011b) Combination treatment in Alzheimer’s disease: results of a randomized, controlled trial with cerebrolysin and donepezil. Curr Alzheimer Res 8:583–591. - PubMed
    1. Alvarez XA, Alvarez I, Iglesias O, Crespo I, Figueroa J, Aleixandre M, Linares C, Granizo E, Garcia-Fantini M, Marey J, Masliah E, Winter S, Muresanu D, Moessler H (2016) Synergistic increase of serum BDNF in Alzheimer patients treated with cerebrolysin and donepezil: association with cognitive improvement in ApoE4 cases. Int J Neuropsychopharmacol 19:1–6. - PMC - PubMed
    1. Alvarez XA, Alvarez I, Aleixandre M, Linares C, Muresanu D, Winter S, Moessler H (2018) Severity-related increase and cognitive correlates of serum VEGF levels in Alzheimer’s disease ApoE4 carriers. J Alzheimers Dis 63:1003–1013. - PubMed

Publication types

MeSH terms